Vitamin D3 differentially regulates parathyroid hormone/parathyroid hormone-related peptide receptor expression in bone and cartilage

Amizuka, Norio; Kwan, Mei; Goltzman, David; Ozawa, Hiroki; White, John H.

doi:10.1172/jci3265

Cited by 49 publications

(35 citation statements)

References 66 publications

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“…Enzyme histochemistry for tartrate-resistant acid phosphatase (TRAP), and immunohistochemistry for sclerostin, DMP-1, ER, osteopontin and RANKL Tartrate-resistant acid phosphatase (TRAP) was detected as previously described [36]; briefly, For immunohistochemistry, dewaxed paraffin sections were used for detection of sclerostin, DMP-1 and osteopontin as previously reported [30,37]. Endogenous peroxidase inhibition was conducted for all sections, and that was the first step in staining unless otherwise stated.…”

Section: Animals and Tissue Preparationmentioning

confidence: 99%

Immunolocalization of sclerostin synthesized by osteocytes in relation to bone remodeling in the interradicular septa of ovariectomized rats

Guo

Liu

et al. 2012

Journal of Electron Microscopy

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This study aimed to elucidate whether estrogen deficiency would affect the synthesis of an osteocyte-derived factor, sclerostin, in the mesial region of alveolar bone. Eight 9-week-old Wister female rats were ovariectomized (OVX), and the other eight rats were Sham-operated (Sham). After 4 weeks, the interradicular septa of mandibular first molar were embedded in paraffin, and then, were histochemically examined. Sclerostin-positive osteocytes were located in a superficial layer of the mesial region of Sham bone, while the OVX mesial region showed a lesser presence of the sclerostin-reactive osteocytes. There was no significant difference in the distribution of estrogen receptor  and TUNEL-positive cells in either Sham or OVX groups. Meanwhile, the Sham mesial region demonstrated many osteoclasts, but the OVX specimens showed numerous osteoclasts in association with intense immunolabeling of the receptor activator of the nuclear factor kB ligand. Complex meshwork of cement lines was seen consistent with irregularly-distributed osteocytic lacunar-canalicular system in the OVX mesial region, compared with those of the Sham specimens. In conclusion, estrogen deficiency appears to inhibit osteocytes for sclerostin synthesis in the mesial region of the interradicular septum, mediated by accelerated bone remodeling, rather than by directly effecting osteocytes. words

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Section: Animals and Tissue Preparationmentioning

confidence: 99%

Immunolocalization of sclerostin synthesized by osteocytes in relation to bone remodeling in the interradicular septa of ovariectomized rats

Guo

Liu

et al. 2012

Journal of Electron Microscopy

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“…Prehypertrophic chondrocytes are the primary target cells for PTHrP and PTH. Chondrocytes temporospatially express PPR, during the proliferative and prehypertrophic stages, partially regulating normal chondrocyte differentiation and tissue function (Lee et al, 1995;Amizuka et al, 1999).…”

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confidence: 99%

PTH Stimulated Growth and Decreased Col‐X Deposition are Phosphotidylinositol‐3,4,5 Triphosphate Kinase and Mitogen Activating Protein Kinase Dependent in Avian Sterna

Harrington¹,

Coon²,

Kern³

et al. 2010

The Anatomical Record

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Type X collagen (Col-X) deposition is a marker of terminal differentiation during chondrogenesis, in addition to appositional growth and apoptosis. The parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) receptor, or PPR, is a G-Protein coupled receptor (GPCR), which activates several downstream pathways, moderating chondrocyte differentiation, including suppression of Col-X deposition. An Avian sterna model was used to analyze the PPR GPCR downstream kinase role in growth rate and extracellular matrix (ECM) including Col-II, IX, and X. Phosphatidylinositol kinase (PI3K), mitogen activating protein kinase (MAPK) and protein kinase A (PKA) were inhibited with specific established inhibitors LY294002, PD98059, and H89, respectively to test the hypothesis that they could reverse/inhibit the PTH/PTHrP pathway. Excised E14 chick sterna were PTH treated with or without an inhibitor and compared to controls. Sternal length was measured every 24 hr. Cultured sterna were immuno-stained using specific antibodies for Col-II, IX, or X and examined via confocal microscopy. Increased growth in PTHtreated sterna was MAPK, PI3K, and PKA dose dependent, suggesting growth was regulated through multiple pathways. Col-X deposition was rescued in PTH-treated sterna in the presence of PI3K or MAPK inhibitors, but not with the PKA inhibitor. All three inhibitors moderately disrupted Col-II and Col-IX deposition. These results suggest that PTH can activate multiple pathways during chondrocyte differentiation. Anat Rec,

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“…Indeed, retinoic acid-induced expression of PTHR1 expression mediated by P2 promoter has been demonstrated in P19 EC mouse cells (Karperien et al 1999). Similarly, it has been demonstrated that in rodents, vitamin D3 administration down-regulates PTHR1 gene transcription by inhibiting P2 promoter activity in osteoblasts, but not in chondrocytes (Amizuka et al 1999). Thus these data demonstrated that P2 promoter activity is subjected to regulation, and that this control may be cell-type specific.…”

Section: Introductionmentioning

confidence: 56%

“…Thus, P1 and P3 promoter activities appear to be tissue-and species-specific. Transcripts derived from P2 promoter can be detected in humans and in rodents in numerous fetal and adult tissues, including cartilage and bone (Bettoun et al 1998, Amizuka et al 1999, Minagawa et al 2000. Although tissue-and species-specific PTHR1 promoter activity is described, the genes encoding for PTHR1 in different species are highly homologous (Kong et al 1994), and the broad PTHR1 expression is mostly attributed to P2 activity (McCuaig et al 1995.…”

Section: Introductionmentioning

confidence: 99%

Functional importance of Myc-associated zinc finger protein for the human parathyroid hormone (PTH)/PTH-related peptide receptor-1 P2 promoter constitutive activity

Leroy

Manen²,

Rizzoli³

et al. 2004

Journal of Molecular Endocrinology

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The aim of the present study was to analyze the functional importance for the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTHR1) gene P2 promoter activity of the putative proximal Myc-associated zinc finger protein (MAZ) site localized at position bp −45 to −39 bp, taking advantage of a G/A mutation identified at position −40 in the human sequence. Wild-type 'full-length' (1285P2) and truncated (760P2) promoter sequences were inserted upstream to the luciferase basic (pLucB) and enhancer (pLucE) reporter gene expression vectors. Transient transfections in osteoblast-like SaOS-2 cells and renal cells (RC.SV3A2) showed that the −40 G/A mutation significantly impaired transcriptional activity of wild-type 1285P2-pLucB and 760P2-pLucE promoter constructs. Further truncation of the P2 sequence demonstrated that the sequence −109/−37 bp was essential for promoter activity. Co-transfection with a MAZ expression vector did not modify the wild-type 1285P2-pLucB construct reporter activity but significantly increased 2-fold the mutated construction activity (P<0·05). Electrophoretic mobility shift assays using SaOS-2 nuclear extracts and a double-stranded DNA fragment encompassing the −45 to −39 putative MAZ site (ds-MAZ-oligo) disclosed two specific DNA-protein complexes. Complex II (fast moving) had a lower affinity for the mutated MAZ motif than for the wild-type MAZ motif while complex I (slow moving) had the same affinity for both wild-type or mutated MAZ sequences. Competition studies with Sp1 consensus oligonucleotide (ds-Sp1-oligo) markedly reduced complex I intensity, with a concomitant increase in that of complex II. Finally, ribonuclease protection assays showed that P2-specific PTHR1 mRNA transcript expression was significantly decreased in SaOS-2 cells transfected with ds-MAZ-oligo as compared with that for control (P<0·001) and ds-Sp1-oligo (P<0·05). Taken together, our studies suggest that the putative −45 to −39 MAZ-binding site regulates the constitutive activity of human PTHR1 P2 promoter.

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Vitamin D3 differentially regulates parathyroid hormone/parathyroid hormone-related peptide receptor expression in bone and cartilage

Cited by 49 publications

References 66 publications

Immunolocalization of sclerostin synthesized by osteocytes in relation to bone remodeling in the interradicular septa of ovariectomized rats

Immunolocalization of sclerostin synthesized by osteocytes in relation to bone remodeling in the interradicular septa of ovariectomized rats

PTH Stimulated Growth and Decreased Col‐X Deposition are Phosphotidylinositol‐3,4,5 Triphosphate Kinase and Mitogen Activating Protein Kinase Dependent in Avian Sterna

Functional importance of Myc-associated zinc finger protein for the human parathyroid hormone (PTH)/PTH-related peptide receptor-1 P2 promoter constitutive activity

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